The general aim in this project is to apply physicochemical techniques and principles to a wide variety of biochemical and biological processes. Although our efforts will continue, as in the past, to be centered on the determination and interpretation of the thermodynamics of such processes, it is frequently found that significant non-thermodynamic results are obtained. It is expected that during the next few years, the work supported by this grant will be concerned primarily with applications of high sensitivity differential scanning calorimetry (DSC) co the study of proteins, nucleic acids and lipids. The power of this technique is at present being rapidly expanded. In the case of proteins, major effort will go into accurate determinations of the thermodynamics of unfolding of numerous mutant forms of a wide variety of proteins, supplied mostly by collaborators in other laboratories. Included will be the lysozyme of T4 phage, staphylococcal nuclease, yeast cytochrome c, ribonuclease T1, gene 32 protein of T4, tryptophan repressor of E. coli, etc. Work on the thermodynamics of the B-Z transition of DNA, and on the extensive polymorphism of DNA indicated/by recent DSC experiments, will be continued. DSC is an excellent technique for studying the phase transitions of phospholipid bilayers, and we will continue to apply DSC to pure lipids and their mixtures with other lipids, drugs, proteins and other types of added solutes. The DSC work will be paralled as appropriate by isothermal calorimetry and other types of measurements.